PIN1

Summary

PIN1 (peptidylprolyl cis/trans isomerase, NIMA-interacting 1, HGNC:8988) is a protein-coding gene on chromosome 19p13, encoding Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Q13526). Peptidyl-prolyl cis/trans isomerase (PPIase) that binds to and isomerizes specific phosphorylated Ser/Thr-Pro (pSer/Thr-Pro) motifs.

Peptidyl-prolyl cis/trans isomerases (PPIases) catalyze the cis/trans isomerization of peptidyl-prolyl peptide bonds. This gene encodes one of the PPIases, which specifically binds to phosphorylated ser/thr-pro motifs to catalytically regulate the post-phosphorylation conformation of its substrates. The conformational regulation catalyzed by this PPIase has a profound impact on key proteins involved in the regulation of cell growth, genotoxic and other stress responses, the immune response, induction and maintenance of pluripotency, germ cell development, neuronal differentiation, and survival. This enzyme also plays a key role in the pathogenesis of Alzheimer’s disease and many cancers. Multiple alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 5300 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 21 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006221

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8988
Approved symbol	PIN1
Name	peptidylprolyl cis/trans isomerase, NIMA-interacting 1
Location	19p13
Locus type	gene with protein product
Status	Approved
Aliases	dod
Ensembl gene	ENSG00000127445
Ensembl biotype	protein_coding
OMIM	601052
Entrez	5300

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 5 protein_coding, 5 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000247970, ENST00000380889, ENST00000585442, ENST00000586025, ENST00000586352, ENST00000587625, ENST00000588695, ENST00000589058, ENST00000590540, ENST00000591777, ENST00000592184, ENST00000929405, ENST00000929406

RefSeq mRNA: 1 — MANE Select: NM_006221 NM_006221

CCDS: CCDS12220

Canonical transcript exons

ENST00000247970 — 4 exons

Exon	Start	End
ENSE00000000225	9835318	9835402
ENSE00003600061	9849090	9849689
ENSE00003652674	9838436	9838648
ENSE00003678420	9848030	9848140

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 98.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.1397 / max 484.5806, expressed in 1822 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173708	40.1397	1822

Top tissues by expression

298 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	98.93	gold quality
frontal pole	UBERON:0002795	98.90	gold quality
prefrontal cortex	UBERON:0000451	98.82	gold quality
anterior cingulate cortex	UBERON:0009835	98.64	gold quality
cingulate cortex	UBERON:0003027	98.63	gold quality
right testis	UBERON:0004534	98.36	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.33	gold quality
left testis	UBERON:0004533	98.30	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.09	gold quality
nucleus accumbens	UBERON:0001882	98.08	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.03	gold quality
pons	UBERON:0000988	98.00	gold quality
cerebellar hemisphere	UBERON:0002245	97.99	gold quality
amygdala	UBERON:0001876	97.95	gold quality
cerebellar cortex	UBERON:0002129	97.93	gold quality
caudate nucleus	UBERON:0001873	97.92	gold quality
frontal cortex	UBERON:0001870	97.81	gold quality
frontal lobe	UBERON:0016525	97.81	gold quality
neocortex	UBERON:0001950	97.68	gold quality
putamen	UBERON:0001874	97.53	gold quality
middle frontal gyrus	UBERON:0002702	97.49	gold quality
cerebellum	UBERON:0002037	97.28	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.23	gold quality
apex of heart	UBERON:0002098	97.08	gold quality
cerebral cortex	UBERON:0000956	97.00	gold quality
telencephalon	UBERON:0001893	96.95	gold quality
paraflocculus	UBERON:0005351	96.91	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.71	gold quality
lower esophagus	UBERON:0013473	96.69	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.01
E-MTAB-7316	yes	8.03

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

6 targets.

Target	Regulation
CCND1	Activation
FN1	Activation
IFNB1	Repression
MYC	Activation
PPARD	Activation
SMAD2	Unknown

Upstream regulators (CollecTRI, top): AR, CEBPA, CEBPG, E2F1, EGR1, FOS, JUN, NFKB, NOTCH1, NR4A1, PITX1, RELA, SMAD2, SMAD3, SPI1, TFAP4, TFCP2

miRNA regulators (miRDB)

29 targeting PIN1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-708-3P	97.50	68.67	1082
HSA-MIR-6890-3P	97.50	65.71	997
HSA-MIR-4693-5P	97.35	67.02	1234
HSA-MIR-152-5P	96.42	66.59	960
HSA-MIR-7160-3P	96.40	64.15	462
HSA-MIR-203A-5P	96.33	65.03	714
HSA-MIR-6861-5P	96.23	67.19	800

Literature-anchored findings (GeneRIF, showing 40)

• binds phosphorylated hSpt5 (PMID:11575923)
• induction of expression by IGF-1 and role in promoting cell cycle S-phase entry (PMID:11787050)
• Interactions between protein kinase CK2 and Pin1. Evidence for phosphorylation-dependent interactions. (PMID:11940573)
• A signaling mechanism is proposed, whereby Pin1 specifically isomerizes only the phosphorylated Ser/Thr-Pro bonds in proteins, regulating protein function by inducing conformational changes following phosphorylation. (PMID:11978535)
• conformational change of Bcl2 due to association with peptidyl prolyl isomerase can contribute to irreversible apoptotic signaling. (PMID:11988841)
• Pin1 is an E2F target gene that is essential for the Neu/Ras-induced transformation of mammary epithelial cells through activation of cyclin D1 (PMID:12101225)
• 1H, 13C and 15N backbone resonance assignment of the peptidyl-prolyl cis-trans isomerase Pin1. (PMID:12153046)
• role in regulating p53 function during DNA damage (PMID:12388558)
• The prolyl isomerase Pin1 is a regulator of p53 in genotoxic response (PMID:12397361)
• following stress-induced phosphorylation, p53 needs to form a complex with Pin1 and to undergo a conformational change to fulfil its biological roles (PMID:12397362)
• Neurons containing Pin1 granules were devoid of neurofibrillary tangles. Granular accumulation of Pin1 may correspond to an absence of neurofibrillary lesions in these cells and might be associated with other mechanisms of neuronal degeneration. (PMID:12410395)
• Pin1 is overexpressed in oral squamous cell carcinoma and its levels correlate with cyclin D1 overexpression (PMID:12579289)
• Peptide binding induces large scale changes in inter-domain mobility in human Pin1 (PMID:12686540)
• analysis of pin1 domain architecture and substrate binding (PMID:12721297)
• Pin1 is a regulator of Cyclin D1 expression in oral squamous cell carcinoma and might have a role in oncogenesis (PMID:12792768)
• Appearance of Pin1 granules in the early stages of Alzheimer’s disease, Pick’s disease, and FTDP-17 (P301L) tauopathy implicates Pin1 in their pathogenesis, but not in progressive supranuclear palsy. (PMID:14572447)
• Data show that NF-kappaB function is regulated by Pin1-mediated prolyl isomerization and ubiquitin-mediated proteolysis of its p65/RelA subunit. (PMID:14690596)
• An additional interaction site between Pin1 and neuronal Tau protein identified at phospho-Thr212-Pro213 of Tau raises the question of functional cooperativity between the WW and catalytic domain of Pin1 while it interacts with hyperphosphorylated Tau. (PMID:14967043)
• Pin1 can suppress transformed phenotypes and inhibit tumor cell growth (PMID:15111319)
• The ability of c-Abl and p300 to increase p73 stability and transcriptional activity requires Pin1. Pin1 is essential for activation of the apoptotic response by endogenous p73. (PMID:15175157)
• Pin1 redistribution and shortfalls occur in frontotemporal dementias characterized by abnormal protein aggregates of tau and other cytoskeletal proteins. may be unifying, contributory factor towards neuronal death in these dementias. (PMID:15474361)
• Pin1 binding was favored when at least two of the three threonine residues were phosphorylated (PMID:15701524)
• Phosphorylation-dependent prolyl isomerization by Pin1 remains a unique mode for the modulation of signal transduction [review]. (PMID:15867923)
• Taken together, these results provide evidence supporting a direct link between oxidative damage to neuronal Pin1 and the pathobiology of Alzheimer disease. (PMID:15950321)
• Mutations in proline 82 of p53 impair its activation by PIN1 and CHK2 in response to DNA damage. (PMID:15964795)
• We conclude that Pin1 is a very well conserved gene, whose rare nucleotide variations have no effect on the individual genetic risk for AD. (PMID:16095818)
• c-Fos represents a novel target for the isomerizing activity of Pin1, which has a role in the mechanism by which c-Jun and c-Fos cooperate to regulate AP-1-dependent gene transcription (PMID:16123044)
• Overexpression of Pin1 and beta-catenin may be closely related with the development and/or progression of colorectal carcinoma and further supports that Pin1 overexpression might contribute to the upregulation of beta-catenin. (PMID:16124054)
• Thus, Pin1 interacts with C99 and promotes its gamma-cleavage, generating Abeta40 and Abeta42. (PMID:16139797)
• Pin1 functions as a transcriptional coactivator of nuclear receptors by modulating SRC-3 coactivator protein-protein complex formation and by also promoting the turnover of the activated SRC-3 oncoprotein. (PMID:16227615)
• Pin1 is a key mediator of granulocyte-macrophage colony-stimulating factor (GM-CSF) production (PMID:16273101)
• High Pin1 expression in primary prostate cancer markedly inhibits the beta-catenin interaction with androgen receptor. (PMID:16428447)
• Pin1 overexpression correlates with centrosome amplification in breast cancer tissues. (PMID:16449657)
• we found that Pin1 could interact with Nek6, one of the human NIMA-related kinases (Neks). Significant correlations between Nek6 and Pin1 mRNA expression levels in 40 pairs of hepatocellular carcinoma cases. (PMID:16476580)
• Pin1 level was found strongly increased during neuronal differentiation and tightly correlated with Tau dephosphorylation at Thr231 (PMID:16697218)
• two promoter polymorphisms (rs2233678 and rs2233679)in PIN1 do not make a significant contribution to AD risk. (PMID:16701948)
• Pin1 expression is correlated with cyclinD1 expression and may have a role in esophageal squamous cell carcinoma (PMID:16820873)
• High levels of Pin1 expression is associated with salivary adenoid cystic carcinoma (PMID:16865250)
• Pin1 may not play a role in the development or progression of gastric cancer. (PMID:16907857)
• In human neuroblastoma cells, Pin1 is downregulated in response to endoplasmic reticulum stress in neuroblastoma cells. (PMID:16972081)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pin1	ENSDARG00000101915
mus_musculus	Pin1	ENSMUSG00000032171
mus_musculus	Pin1rt1	ENSMUSG00000074997
rattus_norvegicus		ENSRNOG00000085482
drosophila_melanogaster	CG32845	FBGN0052845
caenorhabditis_elegans		WBGENE00022448

Paralogs (1): PIN4 (ENSG00000102309)

Protein

Protein identifiers

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 — Q13526 (reviewed: Q13526)

Alternative names: Peptidyl-prolyl cis-trans isomerase Pin1, Rotamase Pin1

All UniProt accessions (4): Q13526, K7EMU7, K7EN45, K7EP26

UniProt curated annotations — full annotation on UniProt →

Function. Peptidyl-prolyl cis/trans isomerase (PPIase) that binds to and isomerizes specific phosphorylated Ser/Thr-Pro (pSer/Thr-Pro) motifs. By inducing conformational changes in a subset of phosphorylated proteins, acts as a molecular switch in multiple cellular processes. Displays a preference for acidic residues located N-terminally to the proline bond to be isomerized. Regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity. Down-regulates kinase activity of BTK. Can transactivate multiple oncogenes and induce centrosome amplification, chromosome instability and cell transformation. Required for the efficient dephosphorylation and recycling of RAF1 after mitogen activation. Binds and targets PML and BCL6 for degradation in a phosphorylation-dependent manner. Acts as a regulator of JNK cascade by binding to phosphorylated FBXW7, disrupting FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation: degradation of FBXW7 leads to subsequent stabilization of JUN. May facilitate the ubiquitination and proteasomal degradation of RBBP8/CtIP through CUL3/KLHL15 E3 ubiquitin-protein ligase complex, hence favors DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR). Upon IL33-induced lung inflammation, catalyzes cis-trans isomerization of phosphorylated IRAK3/IRAK-M, inducing IRAK3 stabilization, nuclear translocation and expression of pro-inflammatory genes in dendritic cells. Catalyzes cis-trans isomerization of phosphorylated phosphoglycerate kinase PGK1 under hypoxic conditions to promote its binding to the TOM complex and targeting to the mitochondrion. Acts as a negative regulator of adipocyte browning by binding to phosphorylated PRDM16, targeting PRDM16 for degradation.

Subunit / interactions. Interacts with STIL. Interacts with KIF20B. Interacts with NEK6. Interacts (via WW domain) with PRKX. Interacts with BTK. Interacts (via PpiC domain) with DAPK1. Interacts with the phosphorylated form of RAF1. Interacts (via WW domain) with ATCAY; upon NGF stimulation. Interacts with PML (isoform PML-4). Interacts with BCL6. Interacts with FBXW7, disrupting FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation. Directly interacts with RBBP8/CtIP; this interaction depends upon RBBP8 phosphorylation. Interacts (via WW domain) with IRAK3/IRAK-M (when phosphorylated at ‘Ser-110’) in response to IL33-mediated (but not TLR4 ligand LPS) dendritic cell stimulation. Interacts with PGK1 (when phosphorylated at ‘Ser-203’); the interaction is direct, occurs under hypoxic conditions, and targets PGK1 to the mitochondrion by promoting interactions with the TOM complex. Interacts with PRDM16 (when phosphorylated); the interaction promotes PRDM16 degradation.

Subcellular location. Nucleus. Nucleus speckle. Cytoplasm.

Tissue specificity. Expressed in immune cells in the lung (at protein level). The phosphorylated form at Ser-71 is expressed in normal breast tissue cells but not in breast cancer cells.

Post-translational modifications. Phosphorylation at Ser-71 by DAPK1 results in inhibition of its catalytic activity, nuclear localization, and its ability to induce centrosome amplification, chromosome instability and cell transformation. Ser-71 is dephosphorylated upon IL33-stimulation of dendritic cells.

Domain organisation. The WW domain is required for the interaction with STIL and KIF20B.

RefSeq proteins (1): NP_006212* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000297	PPIase_PpiC	Domain
IPR001202	WW_dom	Domain
IPR023058	PPIase_PpiC_CS	Conserved_site
IPR036020	WW_dom_sf	Homologous_superfamily
IPR046357	PPIase_dom_sf	Homologous_superfamily
IPR051370	PPIase_Pin1	Family

Pfam: PF00397, PF00639

Enzyme classification (BRENDA):

• EC 5.2.1.8 — peptidylprolyl isomerase (BRENDA: 69 organisms, 374 substrates, 222 inhibitors, 24 Km, 30 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
N-SUCCINYL-ALA-GLU-(TRANS)-PRO-PHE-4-NITROANILID	0.17–0.7	5
N-SUCCINYL-ALA-ALA-(CIS)-PRO-PHE-4-NITROANILIDE	0.104–0.814	2
RNASE T1	0.0004–0.0006	2
SUCCINYL-ALA-ALA-PRO-PHE 4-NITROANILIDE	0.451–1.247	2
SUCCINYL-ALA-LYS-PRO-PHE-4-NITROANILIDE	0.585–0.788	2
ALA-GLY-PSI[CS-N]-PRO-PHE-4-NITROANILIDE	0.53	1
N-SUCCINYL-ALA-LEU-(CIS)-PRO-PHE-4-NITROANILIDE	0.059	1
SUCCINYL-ALA-GLU-PRO-PHE-7-AMIDO-4-METHYLCOUMARI	0.12	1
TRYWNAKMK-(CIS)-PFIFGA	2	1
SUCCINYL-ALA-ALA-(CIS)-PRO-LYS-4-METHYLCOUMARIN-	—	0
SUCCINYL-ALA-ALA-(CIS)-PRO-PHE 4-METHYLCOUMARIN	—	0

Catalyzed reactions (Rhea), 1 shown:

• [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0) (RHEA:16237)

UniProt features (34 total): strand 14, mutagenesis site 5, helix 5, modified residue 4, domain 2, turn 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

186 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7AZ2	X-RAY DIFFRACTION	1.08
7AZ1	X-RAY DIFFRACTION	1.15
3I6C	X-RAY DIFFRACTION	1.3
4TNS	X-RAY DIFFRACTION	1.33
1PIN	X-RAY DIFFRACTION	1.35
3TC5	X-RAY DIFFRACTION	1.4
7AXN	X-RAY DIFFRACTION	1.4
7BG3	X-RAY DIFFRACTION	1.4
6VAJ	X-RAY DIFFRACTION	1.42
9KFZ	X-RAY DIFFRACTION	1.43
2ITK	X-RAY DIFFRACTION	1.45
2ZQT	X-RAY DIFFRACTION	1.46
2F21	X-RAY DIFFRACTION	1.5
2Q5A	X-RAY DIFFRACTION	1.5
5VTJ	X-RAY DIFFRACTION	1.5
7AOG	X-RAY DIFFRACTION	1.5
9JJS	X-RAY DIFFRACTION	1.52
9KEQ	X-RAY DIFFRACTION	1.53
9KX7	X-RAY DIFFRACTION	1.53
9KXC	X-RAY DIFFRACTION	1.53
9JZ2	X-RAY DIFFRACTION	1.55
9KG9	X-RAY DIFFRACTION	1.55
9KFC	X-RAY DIFFRACTION	1.56
6O34	X-RAY DIFFRACTION	1.57
8VJD	X-RAY DIFFRACTION	1.57
9KXJ	X-RAY DIFFRACTION	1.57
8VJG	X-RAY DIFFRACTION	1.58
9KXG	X-RAY DIFFRACTION	1.58
6DUN	X-RAY DIFFRACTION	1.59
7NJ6	X-RAY DIFFRACTION	1.59

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13526-F1	92.57	0.88

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 43, 46, 71, 108

Mutagenesis-validated functional residues (5):

Position	Phenotype
63	loss of peptidyl-prolyl cis/trans isomerase activity. no effect on the interaction with irak3/irak-m. abolishes il33-med
71	loss of peptidyl-prolyl cis/trans isomerase activity, nuclear localization and cellular function.
113	loss of peptidyl-prolyl cis/trans isomerase activity; decrease in dna repair of double-strand breaks by homologous recom
23	reduced affinity for kif20b.
34	loss of binding to phosphorylated target proteins, including to phosphorylated rbbp8/ctip; decrease in dna repair of dou

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-5668599	RHO GTPases Activate NADPH Oxidases
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-6811555	PI5P Regulates TP53 Acetylation
R-HSA-936440	Negative regulators of DDX58/IFIH1 signaling

MSigDB gene sets: 274 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_PHOSPHORYLATION, MACLACHLAN_BRCA1_TARGETS_DN, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_NEGATIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_PROTEIN_TARGETING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_NEUROGENESIS

GO Biological Process (24): protein peptidyl-prolyl isomerization (GO:0000413), response to hypoxia (GO:0001666), positive regulation of protein phosphorylation (GO:0001934), obsolete protein targeting to mitochondrion (GO:0006626), regulation of mitotic nuclear division (GO:0007088), Rho protein signal transduction (GO:0007266), regulation of gene expression (GO:0010468), neuron differentiation (GO:0030182), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), regulation of protein stability (GO:0031647), protein destabilization (GO:0031648), regulation of cytokinesis (GO:0032465), negative regulation of protein catabolic process (GO:0042177), positive regulation of transcription by RNA polymerase II (GO:0045944), synapse organization (GO:0050808), protein stabilization (GO:0050821), negative regulation of SMAD protein signal transduction (GO:0060392), negative regulation of ERK1 and ERK2 cascade (GO:0070373), cellular response to hypoxia (GO:0071456), positive regulation of canonical Wnt signaling pathway (GO:0090263), regulation of protein localization to nucleus (GO:1900180), negative regulation of amyloid-beta formation (GO:1902430), negative regulation of brown fat cell differentiation (GO:1903444), negative regulation of cell motility (GO:2000146)

GO Molecular Function (13): peptidyl-prolyl cis-trans isomerase activity (GO:0003755), cytoskeletal motor activity (GO:0003774), beta-catenin binding (GO:0008013), cis-trans isomerase activity (GO:0016859), mitogen-activated protein kinase kinase binding (GO:0031434), GTPase activating protein binding (GO:0032794), tau protein binding (GO:0048156), phosphoserine residue binding (GO:0050815), phosphothreonine residue binding (GO:0050816), phosphoprotein binding (GO:0051219), ubiquitin ligase activator activity (GO:1990757), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear speck (GO:0016607), midbody (GO:0030496), ciliary basal body (GO:0036064), glutamatergic synapse (GO:0098978), postsynaptic cytosol (GO:0099524)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Antimicrobial mechanism of IFN-stimulated genes	1
RHO GTPase Effectors	1
Regulation of TP53 Activity	1
Regulation of TP53 Activity through Acetylation	1
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein binding	3
regulation of cell cycle process	2
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	2
regulation of protein stability	2
protein phosphorylated amino acid binding	2
peptidyl-proline modification	1
response to stress	1
response to decreased oxygen levels	1
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
regulation of mitotic cell cycle	1
regulation of nuclear division	1
mitotic nuclear division	1
small GTPase-mediated signal transduction	1
gene expression	1
regulation of macromolecule biosynthetic process	1
cell differentiation	1
generation of neurons	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
regulation of biological quality	1
cytokinesis	1
regulation of cell division	1
negative regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
negative regulation of protein metabolic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cell junction organization	1
regulation of SMAD protein signal transduction	1
SMAD protein signal transduction	1
negative regulation of intracellular signal transduction	1
negative regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1

Protein interactions and networks

STRING

3035 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIN1	FKBP1C	Q5VVH2	672
PIN1	TP53	P04637	607
PIN1	MYC	P01106	601
PIN1	CCND1	P24385	597
PIN1	PLK1	P53350	537
PIN1	IRF3	Q14653	534
PIN1	HIPK2	Q9H2X6	532
PIN1	SPNS1	Q9H2V7	518
PIN1	CDK10	Q15131	495
PIN1	FKBP2	P26885	489
PIN1	TRIM26	Q12899	487
PIN1	CTDP1	Q9Y5B0	480
PIN1	TRIM59	Q8IWR1	473
PIN1	NCOR2	Q9Y618	473
PIN1	SSU72	Q9NP77	464

IntAct

792 interactions, top by confidence:

A	B	Type	Score
TRAF2	PIN1	psi-mi:“MI:0915”(physical association)	0.780
TNIP1	PIN1	psi-mi:“MI:0915”(physical association)	0.780
MDFI	PIN1	psi-mi:“MI:0915”(physical association)	0.780
TSC22D4	PIN1	psi-mi:“MI:0915”(physical association)	0.780
PIN1	MDFI	psi-mi:“MI:0915”(physical association)	0.780
PIN1	TRAF2	psi-mi:“MI:0915”(physical association)	0.780
PIN1	FOXP2	psi-mi:“MI:0915”(physical association)	0.720
PIN1	KRT38	psi-mi:“MI:0915”(physical association)	0.720
PIN1	NUP62	psi-mi:“MI:0915”(physical association)	0.720
PIN1	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.720
GOLGA2	PIN1	psi-mi:“MI:0915”(physical association)	0.720
PIN1	KRT31	psi-mi:“MI:0915”(physical association)	0.720
NAB2	PIN1	psi-mi:“MI:0915”(physical association)	0.720
PIN1	CCDC184	psi-mi:“MI:0915”(physical association)	0.720
ANKRD40	PIN1	psi-mi:“MI:0915”(physical association)	0.720
CEP76	PIN1	psi-mi:“MI:0915”(physical association)	0.720
CNKSR1	PIN1	psi-mi:“MI:0915”(physical association)	0.720
ZNF446	PIN1	psi-mi:“MI:0915”(physical association)	0.720
ZBTB9	PIN1	psi-mi:“MI:0915”(physical association)	0.720
PIN1	HEXIM2	psi-mi:“MI:0915”(physical association)	0.720
PIN1	SSBP3	psi-mi:“MI:0915”(physical association)	0.720
PIN1	IKZF3	psi-mi:“MI:0915”(physical association)	0.720
FOXP2	PIN1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (560): PIN1 (Two-hybrid), PIN1 (Two-hybrid), PIN1 (Two-hybrid), PIN1 (Two-hybrid), PIN1 (Two-hybrid), PIN1 (Two-hybrid), PIN1 (Two-hybrid), PIN1 (Two-hybrid), RBBP8 (Two-hybrid), TCF4 (Two-hybrid), TRAF1 (Two-hybrid), TRAF2 (Two-hybrid), TRIP6 (Two-hybrid), ZBTB14 (Two-hybrid), KRT38 (Two-hybrid)

ESM2 similar proteins: O04287, O42123, O42993, O94746, P0A0W2, P0A0W3, P0C1J3, P0CP94, P0CP95, P0CY37, P18203, P20080, P20081, P26883, P28725, P28870, P48375, P56989, P62942, P62943, P68106, P68107, P97534, Q13526, Q2U316, Q2UPT7, Q38931, Q43207, Q4HZB8, Q4R383, Q4W9R2, Q4WHX4, Q4WLV6, Q554J3, Q5ATN7, Q5BIN5, Q5VVH2, Q62658, Q6BX45, Q6CF41

Diamond homologs: A1CQG2, A1D3C5, A2A5Z6, A2QQ28, A9JRZ0, B0XQ72, B4F6W9, B8N7E5, D3ZBM7, E1B7Q7, E1C656, F1LP64, F1N6G5, F1RCR6, F8W2M1, G0S9J5, G5E870, O00308, O08759, O13834, O14326, O15033, O17736, O95714, P39940, P40985, P46934, P46935, P51593, P53119, Q03280, Q05086, Q08CZ0, Q09291, Q0CCL1, Q13526, Q14669, Q15034, Q15386, Q15751

SIGNOR signaling

19 interactions.

A	Effect	B	Mechanism
PRKACA	“down-regulates activity”	PIN1	phosphorylation
STIL	up-regulates	PIN1	binding
PLK1	up-regulates	PIN1	phosphorylation
NOTCH1	“up-regulates quantity by expression”	PIN1	“transcriptional regulation”
PIN1	up-regulates	NOTCH1	binding
PIN1	up-regulates	MYC	binding
AURKA	“down-regulates activity”	PIN1	phosphorylation
MAP3K11	up-regulates	PIN1	phosphorylation
PIN1	“down-regulates quantity by destabilization”	IRF3	binding
PIN1	“down-regulates quantity by repression”	IFNB1	“transcriptional regulation”
NOTCH	“up-regulates quantity by expression”	PIN1	“transcriptional regulation”
“diarsenic trioxide”	“down-regulates activity”	PIN1	“chemical inhibition”
“all-trans-retinoic acid”	“down-regulates activity”	PIN1	“chemical inhibition”
PIN1	“down-regulates activity”	XPO5	isomerization
PIN1	“up-regulates activity”	IRS1	isomerization
PIN1	“down-regulates quantity by destabilization”	KLF10	binding
MAPK8	“up-regulates quantity by stabilization”	PIN1	phosphorylation
MAPK9	“up-regulates quantity by stabilization”	PIN1	phosphorylation
DAPK1	“down-regulates activity”	PIN1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

21 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

862 predictions. Top by Δscore:

Variant	Effect	Δscore
19:9835398:C:G	donor_gain	1.0000
19:9838430:CTCCA:C	acceptor_loss	1.0000
19:9838431:TCCA:T	acceptor_loss	1.0000
19:9838432:CCA:C	acceptor_loss	1.0000
19:9838433:CA:C	acceptor_loss	1.0000
19:9838434:A:AG	acceptor_gain	1.0000
19:9838434:AGG:A	acceptor_loss	1.0000
19:9838435:G:GG	acceptor_gain	1.0000
19:9838435:GGCC:G	acceptor_gain	1.0000
19:9838646:ACG:A	donor_gain	1.0000
19:9838648:GGT:G	donor_loss	1.0000
19:9838649:G:GG	donor_gain	1.0000
19:9838650:T:A	donor_loss	1.0000
19:9835401:AG:A	donor_loss	0.9900
19:9835404:T:G	donor_loss	0.9900
19:9838434:AGGCC:A	acceptor_gain	0.9900
19:9838435:GGC:G	acceptor_gain	0.9900
19:9838435:GGCCG:G	acceptor_gain	0.9900
19:9838647:CG:C	donor_gain	0.9900
19:9838648:GG:G	donor_gain	0.9900
19:9848020:AT:A	acceptor_gain	0.9900
19:9848021:T:G	acceptor_gain	0.9900
19:9848027:CAG:C	acceptor_loss	0.9900
19:9848028:A:AG	acceptor_gain	0.9900
19:9848028:A:T	acceptor_loss	0.9900
19:9848029:G:GG	acceptor_gain	0.9900
19:9848029:GGCT:G	acceptor_gain	0.9900
19:9848116:G:T	donor_gain	0.9900
19:9848138:GAG:G	donor_gain	0.9900
19:9848150:G:GT	donor_gain	0.9900

AlphaMissense

1067 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:9835375:T:A	W11R	1.000
19:9835375:T:C	W11R	1.000
19:9835377:G:C	W11C	1.000
19:9835377:G:T	W11C	1.000
19:9838477:T:A	W34R	1.000
19:9838477:T:C	W34R	1.000
19:9838479:G:C	W34C	1.000
19:9838479:G:T	W34C	1.000
19:9838548:C:G	C57W	1.000
19:9838552:C:A	H59N	1.000
19:9838552:C:G	H59D	1.000
19:9838559:T:A	L61Q	1.000
19:9838559:T:C	L61P	1.000
19:9838564:A:G	K63E	1.000
19:9838566:G:C	K63N	1.000
19:9838566:G:T	K63N	1.000
19:9848078:C:A	A107D	1.000
19:9848089:A:C	S111R	1.000
19:9848090:G:T	S111I	1.000
19:9848091:C:A	S111R	1.000
19:9848091:C:G	S111R	1.000
19:9848093:A:T	D112V	1.000
19:9848095:T:C	C113R	1.000
19:9848116:G:A	G120R	1.000
19:9848116:G:C	G120R	1.000
19:9848117:G:A	G120E	1.000
19:9848117:G:T	G120V	1.000
19:9849170:G:C	G155R	1.000
19:9849170:G:T	G155C	1.000
19:9849171:G:A	G155D	1.000

dbSNP variants (sampled 300 via entrez): RS1000212124 (19:9849703 A>C,T), RS1000294884 (19:9842960 G>C), RS1000501448 (19:9838593 C>G,T), RS1000632387 (19:9844206 C>T), RS1000863402 (19:9839556 G>A), RS1001035888 (19:9845153 G>A,T), RS1001228883 (19:9838299 CATG>C), RS1001251953 (19:9835018 C>A,G,T), RS1001639443 (19:9835183 A>G), RS1002117959 (19:9843404 G>A), RS1002127839 (19:9843637 C>G,T), RS1002323929 (19:9846256 G>A), RS1002510437 (19:9841325 C>T), RS1002607404 (19:9834886 C>G,T), RS1002790927 (19:9841086 T>C,G)

Disease associations

OMIM: gene MIM:601052 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002711_13	Sleep duration	1.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2288 (SINGLE PROTEIN), CHEMBL6066039 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 224,754 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1201207	BETAMETHASONE PHOSPHORIC ACID	4	954
CHEMBL38	TRETINOIN	4	194,008
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL407874	6-O-BENZYLGUANINE	3	6,988

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2233678	Efficacy	3	oxaliplatin	Colorectal Neoplasms
rs2233678	Efficacy	3	irinotecan	Colorectal Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2233678	PIN1	3	3.50	2	oxaliplatin;irinotecan

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Peptidyl-prolyl cis/trans isomerases

Most potent curated ligand interactions (6 total), top 6:

Ligand	Action	Affinity	Parameter
AG-122018	Inhibition	7.92	pKi
BJP-06-005-3	Inhibition	7.82	pKi
AG-17724	Inhibition	7.1	pKi
API-32	Binding	6.81	pKd
compound 20 [PMID: 25091930]	Inhibition	6.71	pKi
sulfopin	Inhibition	6.68	pKi

Binding affinities (BindingDB)

18 measured of 20 human assays (20 total across all organisms); most potent 18 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
3-fluorophenylalanine derivative, 21b	KI	6 nM
3-fluorophenylalanine derivative, 21a	KI	8 nM
3-methylphenylalanine derivative, 22a	KI	32 nM
3-methylphenylalanine derivative, 22b	KI	57 nM
2,3-difluorophenylalanine derivative, 23a	KI	78 nM
2,3-difluorophenylalanine derivative, 23b	KI	89 nM
naphthalene carboxamide, 18a	KI	100 nM
benzothiophene carboxamide, 18b	KI	179 nM
CHEMBL5411977	IC50	440 nM
amide, 17c	KI	525 nM
CHEMBL5406477	IC50	780 nM
pipecolate deriv., 12b	KI	800 nM
CHEMBL5207244	IC50	1690 nM
pipecolate deriv., 11	KI	1700 nM
urea, 17b	KI	4130 nM
sulfonamide, 17a	KI	8770 nM
pipecolate deriv., 12a	KI	9460 nM
CHEMBL3633018	IC50	91000 nM

ChEMBL bioactivities

483 potent at pChembl≥5 of 661 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.92	Ki	1.2	nM	CHEMBL219531
8.92	Ki	1.2	nM	CHEMBL5395865
8.32	Ki	4.8	nM	CHEMBL438271
8.22	IC50	6	nM	CHEMBL585917
8.22	Ki	6	nM	CHEMBL1090715
8.22	Ki	6	nM	CHEMBL585917
8.22	Ki	6	nM	CHEMBL1089602
8.10	Ki	8	nM	CHEMBL1163019
7.92	Ki	12	nM	CHEMBL3353369
7.82	Ki	15	nM	CHEMBL4750217
7.82	Ki	15	nM	CHEMBL6148397
7.77	Ki	17	nM	CHEMBL5397880
7.74	Ki	18.3	nM	CHEMBL436759
7.74	Ki	18.3	nM	CHEMBL5400597
7.70	Ki	20	nM	CHEMBL4751817
7.70	Ki	20	nM	CHEMBL5430490
7.60	IC50	25	nM	CHEMBL2409075
7.60	Kd	25	nM	CHEMBL5591180
7.60	IC50	25	nM	CHEMBL595291
7.52	Ki	30	nM	CHEMBL5405065
7.51	IC50	31	nM	CHEMBL5408559
7.51	IC50	31	nM	CHEMBL1089622
7.50	Ki	32	nM	CHEMBL576239
7.50	IC50	32	nM	CHEMBL1089625
7.48	Kd	33	nM	CHEMBL1089626
7.37	IC50	43	nM	CHEMBL1089623
7.33	Kd	47	nM	CHEMBL1089622
7.32	Ki	48	nM	CHEMBL4750217
7.32	Kd	48	nM	CHEMBL1089623
7.30	Ki	50	nM	CHEMBL2409078
7.30	IC50	50	nM	CHEMBL585917
7.24	Ki	57	nM	CHEMBL583856
7.19	IC50	64.4	nM	CHEMBL6120754
7.17	IC50	67	nM	CHEMBL5075017
7.16	Ki	70	nM	CHEMBL5426583
7.14	Kd	72	nM	CHEMBL3590308
7.14	Kd	72	nM	CHEMBL585944
7.14	IC50	72.3	nM	CHEMBL5427982
7.14	Kd	72	nM	CHEMBL5423483
7.12	Ki	75	nM	CHEMBL3353368
7.12	Ki	76	nM	CHEMBL3322220
7.11	Ki	78	nM	CHEMBL577063
7.10	Ki	80	nM	CHEMBL3322219
7.06	Kd	87	nM	CHEMBL5597140
7.05	IC50	90	nM	CHEMBL1090715
7.05	Ki	89	nM	CHEMBL584271
7.04	IC50	91.4	nM	6-O-BENZYLGUANINE
7.03	Kd	93	nM	CHEMBL5598027
7.00	Ki	100	nM	CHEMBL577299
6.92	Kd	120	nM	CHEMBL3590367

PubChem BioAssay actives

439 with measured affinity, of 995 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[(2R,3R)-3-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-2-acetamidohexanoyl]amino]propanoyl]amino]propanoyl]amino]-3-(1-benzothiophen-3-yl)propanoyl]amino]-4-[(2S)-2-[[(2S)-1-[[(2S)-1,5-diamino-1,5-dioxopentan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]carbamoyl]piperidin-1-yl]-4-oxobutan-2-yl] dihydrogen phosphate	262823: Inhibition of human Pin1 PPIase Activity by protease free PPIase assay	ki	0.0012	uM
[(3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-2-acetamidohexanoyl]amino]propanoyl]amino]propanoyl]amino]-3-(1-benzothiophen-3-yl)propanoyl]amino]-4-[(2S)-2-[[(2S)-1-[[(2S)-1,5-diamino-1,5-dioxopentan-2-yl]amino]-3-naphthalen-1-yl-1-oxopropan-2-yl]carbamoyl]piperidin-1-yl]-4-oxobutan-2-yl] dihydrogen phosphate	1975602: Inhibition of Gst-tagged human Pin1 assessed as inhibition constant by Western blot analysis	ki	0.0012	uM
[(2S,3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-2-acetamidohexanoyl]amino]propanoyl]amino]propanoyl]amino]-3-(4-phenylphenyl)propanoyl]amino]-4-[(2S)-2-[[(2S)-1-[[(2S)-1,5-diamino-1,5-dioxopentan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-4-oxobutan-2-yl] dihydrogen phosphate	262823: Inhibition of human Pin1 PPIase Activity by protease free PPIase assay	ki	0.0048	uM
[(2R)-2-(1-benzothiophene-2-carbonylamino)-3-(3-fluorophenyl)propyl] dihydrogen phosphate	1693196: Inhibition of Pin1 (unknown origin)	ki	0.0060	uM
46883909	474989: Displacement of WFYpSPFLE from human Pin1 catalytic domain after 10-20 mins by fluorescence polarization assay	ki	0.0060	uM
(E,2R)-5-(3-fluorophenyl)-2-(naphthalene-2-carbonylamino)pent-4-enoic acid	1693191: Inhibition of N-terminal His tagged human Pin1 expressed in Escherichia coli BL21 (DE3) using Suc-Ala-Glu-Pro-Phe-4-nitroanilide as substrate preincubated with enzyme for 10 mins followed by substrate addition by UV-Vis spectrophotometer analysis	ki	0.0060	uM
[(2R)-3-(3-fluorophenyl)-2-(naphthalene-2-carbonylamino)propyl] dihydrogen phosphate	1799256: Pin1 Enzymatic Activity Assay from Article 10.1016/j.bmcl.2009.08.034: “Structure-based design of novel human Pin1 inhibitors (I).”	ki	0.0080	uM
[(2S)-3-(3-fluorophenyl)-2-(naphthalene-2-carbonylamino)propyl] dihydrogen phosphate	445464: Displacement of WFYpSPFLE from human Pin1 after 10-20 mins by fluorescence polarization assay	ki	0.0080	uM
(2R)-2-[[2-(9H-fluoren-9-yl)acetyl]amino]-3-(6-fluoro-1H-indol-2-yl)propanoic acid	1186728: Inhibition of Pin1 (unknown origin)	ki	0.0120	uM
ethyl (2S)-5-(carbamoylamino)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[(2-chloroacetyl)-methylamino]-3-phenylpropanoyl]piperidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]pentanoate	1975620: Inhibition of Gst-tagged human Pin1 assessed as inhibition constant measured after 12 hrs by FP binding assay	ki	0.0150	uM
2-chloro-N-(2,2-dimethylpropyl)-N-(1,1-dioxothiolan-3-yl)acetamide	2123916: Binding affinity to GST-tagged PIN1 (unknown origin) using N-terminal fluorescein-labeled Bth-D-pThr-Pip-Nal as substrate assessed as inhibition constant incubated for 14 hrs by fluorescence polarization assay	ki	0.0170	uM
[(3S)-3-[[(2S)-2-acetamidobutanoyl]amino]-4-[(2S)-2-[[(2S)-1-[[(2S)-1,5-diamino-1,5-dioxopentan-2-yl]amino]-3-naphthalen-1-yl-1-oxopropan-2-yl]carbamoyl]piperidin-1-yl]-4-oxobutan-2-yl] dihydrogen phosphate	1975602: Inhibition of Gst-tagged human Pin1 assessed as inhibition constant by Western blot analysis	ki	0.0183	uM
[(2S,3R)-3-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-4-[(2R)-2-[[(2S)-1-[[(2S)-1,5-diamino-1,5-dioxopentan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]carbamoyl]piperidin-1-yl]-4-oxobutan-2-yl] dihydrogen phosphate	262823: Inhibition of human Pin1 PPIase Activity by protease free PPIase assay	ki	0.0183	uM
[(2S,3R)-3-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-4-[(2S)-2-[[(2S)-1-[[(2S)-1,5-diamino-1,5-dioxopentan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]carbamoyl]piperidin-1-yl]-4-oxobutan-2-yl] dihydrogen phosphate	1693192: Inhibition of GST-tagged Pin1 (unknown origin) using Suc-Ala-pSer-Pro-Phe-pNA as substrate preincubated with enzyme for 12 hrs followed by substrate addition by chymotrypsin coupled assay	ki	0.0200	uM
[(2S,3R)-3-[[(2R)-2-aminopropanoyl]amino]-4-[(2R)-2-[[(2R)-1-[[(2R)-1,5-diamino-1,5-dioxopentan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]carbamoyl]piperidin-1-yl]-4-oxobutan-2-yl] dihydrogen phosphate	1975602: Inhibition of Gst-tagged human Pin1 assessed as inhibition constant by Western blot analysis	ki	0.0200	uM
N-[3-[1-[4-(4-cyanophenyl)phenyl]triazol-4-yl]-1-[(1-methylpiperidin-4-yl)amino]-1-oxopropan-2-yl]-1-(2-methylphenyl)cyclopropane-1-carboxamide	2123907: Binding affinity to GST-tagged PIN1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.0250	uM
(2R)-2-[[5-[4-(aminomethyl)phenyl]-2-methylfuran-3-carbonyl]amino]-3-(1H-benzimidazol-2-yl)propanoic acid	761670: Inhibition of Pin1 (unknown origin)	ic50	0.0250	uM
methyl (2R)-2-[[5-[4-(aminomethyl)phenyl]-2-methylfuran-3-carbonyl]amino]-3-(1H-benzimidazol-2-yl)propanoate	453509: Inhibition of 8His-tagged Pin1 PPIase domain (45-163)	ic50	0.0250	uM
(4S)-5-[(2S)-2-[[(2S)-1-[[(2S)-1-amino-5-(carbamoylamino)-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamoyl]piperidin-1-yl]-4-[(2-chloroacetyl)amino]-5-oxopentanoic acid	1975620: Inhibition of Gst-tagged human Pin1 assessed as inhibition constant measured after 12 hrs by FP binding assay	ki	0.0300	uM
[(1S)-1-[(3R,9R,12S,15S,18S,21S)-12-(3-amino-3-oxopropyl)-15-[(4-hydroxyphenyl)methyl]-7,9-dimethyl-18-(naphthalen-2-ylmethyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazabicyclo[19.4.0]pentacosan-3-yl]ethyl] dihydrogen phosphate	1975604: Inhibition of Pin1 (unknown origin)	ic50	0.0310	uM
[(1R)-1-[(3R,9S,12S,15S,18S,21S)-12-(3-amino-3-oxopropyl)-15-[(4-hydroxyphenyl)methyl]-7,9-dimethyl-18-(naphthalen-2-ylmethyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazabicyclo[19.4.0]pentacosan-3-yl]ethyl] dihydrogen phosphate	473214: Inhibition of human Pin1 S16A/Y23A mutant expressed in Escherichia coli BL21(DE3) by chymotrypsin-coupled PPIase inhibition assay	ic50	0.0310	uM
[(2R)-3-(3-methylphenyl)-2-(naphthalene-2-carbonylamino)propyl] dihydrogen phosphate	1799256: Pin1 Enzymatic Activity Assay from Article 10.1016/j.bmcl.2009.08.034: “Structure-based design of novel human Pin1 inhibitors (I).”	ki	0.0320	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-acetamido-3-[[3-[[(5R)-6-amino-5-[[3-[(3R,9R,12S,15S,18S,21S)-15-[(4-hydroxyphenyl)methyl]-7,9,19-trimethyl-18-(naphthalen-2-ylmethyl)-2,5,8,11,14,17,20-heptaoxo-3-[(1R)-1-phosphonooxyethyl]-1,4,7,10,13,16,19-heptazabicyclo[19.4.0]pentacosan-12-yl]propanoylamino]methyl]-6-oxohexyl]amino]-3-oxopropyl]disulfanyl]propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoic acid	473214: Inhibition of human Pin1 S16A/Y23A mutant expressed in Escherichia coli BL21(DE3) by chymotrypsin-coupled PPIase inhibition assay	ic50	0.0320	uM
[(1R)-1-[(3R,6R,9R,12S,15S,18S,21S)-12-(3-amino-3-oxopropyl)-6,9,15-tris[3-(diaminomethylideneamino)propyl]-18-(naphthalen-2-ylmethyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazabicyclo[19.4.0]pentacosan-3-yl]ethyl] dihydrogen phosphate	473215: Binding affinity to human Pin1 S16A/Y23A mutant expressed in Escherichia coli BL21(DE3) by isothermal titration colorimetry	kd	0.0330	uM
[(1R)-1-[(3R,9R,12S,15S,18S,21S)-12-(3-amino-3-oxopropyl)-15-(3-aminopropyl)-9-methyl-18-(naphthalen-2-ylmethyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazabicyclo[19.4.0]pentacosan-3-yl]ethyl] dihydrogen phosphate	473214: Inhibition of human Pin1 S16A/Y23A mutant expressed in Escherichia coli BL21(DE3) by chymotrypsin-coupled PPIase inhibition assay	ic50	0.0430	uM
piperidine-1-carbothioyl piperidine-1-carbodithioate	761668: Competitive inhibition of Pin1 (unknown origin) by Lineweaver-Burk plot analysis	ki	0.0500	uM
[(2R)-2-(1-benzothiophene-2-carbonylamino)-3-(3-methylphenyl)propyl] dihydrogen phosphate	1799256: Pin1 Enzymatic Activity Assay from Article 10.1016/j.bmcl.2009.08.034: “Structure-based design of novel human Pin1 inhibitors (I).”	ki	0.0570	uM
8-(2-chloroacetyl)-4-[(5-naphthalen-1-ylfuran-2-yl)methyl]-1-thia-4,8-diazaspiro[4.5]decan-3-one	1819306: Displacement of 5-FITC-(Acp)-Bth-D-pThr-Pip-2-NaI-Q from N-terminal-GST-fused human Pin1 expressed in Escherichia coli BL21(DE3) incubated for 12 hrs by fluorescence polarization assay	ic50	0.0670	uM
(4S)-5-[(2S)-2-[[(2S)-1-[[(2S)-1-amino-5-(carbamoylamino)-1-oxopentan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]carbamoyl]piperidin-1-yl]-4-[(2-chloroacetyl)amino]-5-oxopentanoic acid	1975620: Inhibition of Gst-tagged human Pin1 assessed as inhibition constant measured after 12 hrs by FP binding assay	ki	0.0700	uM
[(2R)-2-(1-benzothiophene-2-carbonylamino)-3-phenylpropyl] dihydrogen phosphate	1724650: Binding affinity to full length Pin 1 (unknown origin) by isothermal titration calorimetry method	kd	0.0720	uM
(2S)-6-amino-2-[[(6R,12R,19R,22S,25S,28S,31R,34S,37S,40S,43S,46S,49S,52S,55S)-37-benzyl-25,43,46,49,52-pentakis(3-carbamimidamidopropyl)-6,8,28,31-tetramethyl-22,40-bis(naphthalen-2-ylmethyl)-4,7,10,13,20,23,26,29,32,35,38,41,44,47,50,53,58,61-octadecaoxo-12-[(1S)-1-phosphonooxyethyl]-5,8,11,14,21,24,27,30,33,36,39,42,45,48,51,54,57,62-octadecazatetracyclo[32.26.3.13,59.014,19]tetrahexaconta-1(60),2,59(64)-triene-55-carbonyl]amino]hexanoic acid	1234326: Binding affinity to N-terminal MBP fused and Texas-red-labeled full-length human Pin1 S16A/Y23A mutant expressed in Escherichia coli assessed as increase in fluorescence anisotropy by spectrofluorimetry	kd	0.0720	uM
[(1S)-1-[(6S,12R,19S,22S,25S,28R,31R,34S,37S,40S,43S,46S,49S,52S,55S)-37-benzyl-25,43,46,49,52-pentakis(3-carbamimidamidopropyl)-55-carbamoyl-6,28,31-trimethyl-22,40-bis(naphthalen-2-ylmethyl)-4,7,10,13,20,23,26,29,32,35,38,41,44,47,50,53,58,61-octadecaoxo-5,8,11,14,21,24,27,30,33,36,39,42,45,48,51,54,57,62-octadecazatetracyclo[32.26.3.13,59.014,19]tetrahexaconta-1(60),2,59(64)-trien-12-yl]ethyl] dihydrogen phosphate	1975607: Inhibition of full length human Pin1 expressed in Escherichia coli assessed as dissociation constant by fluorescence anisotropy binding assay	kd	0.0720	uM
N-[[4-[(2-amino-7H-purin-6-yl)oxymethyl]phenyl]methyl]-2,2,2-trifluoroacetamide	1975604: Inhibition of Pin1 (unknown origin)	ic50	0.0723	uM
(2R)-2-[3-(2,6-dichlorophenyl)propanoylamino]-3-(6-fluoro-1H-indol-2-yl)propanoic acid	1186728: Inhibition of Pin1 (unknown origin)	ki	0.0750	uM
(2R)-2-(1-benzothiophene-2-carbonylamino)-3-(6-fluoro-1H-benzimidazol-2-yl)propanoic acid	1186728: Inhibition of Pin1 (unknown origin)	ki	0.0760	uM
[(2R)-3-(2,3-difluorophenyl)-2-(naphthalene-2-carbonylamino)propyl] dihydrogen phosphate	1799256: Pin1 Enzymatic Activity Assay from Article 10.1016/j.bmcl.2009.08.034: “Structure-based design of novel human Pin1 inhibitors (I).”	ki	0.0780	uM
(2R)-3-(6-fluoro-1H-benzimidazol-2-yl)-2-(naphthalene-2-carbonylamino)propanoic acid	1186728: Inhibition of Pin1 (unknown origin)	ki	0.0800	uM
N-[1-[(1-acetylpiperidin-4-yl)amino]-3-[1-[4-(4-cyanophenyl)phenyl]triazol-4-yl]-1-oxopropan-2-yl]-1-(2-methylphenyl)cyclopropane-1-carboxamide	2123907: Binding affinity to GST-tagged PIN1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.0870	uM
[(2R)-2-(1-benzothiophene-2-carbonylamino)-3-(2,3-difluorophenyl)propyl] dihydrogen phosphate	1799256: Pin1 Enzymatic Activity Assay from Article 10.1016/j.bmcl.2009.08.034: “Structure-based design of novel human Pin1 inhibitors (I).”	ki	0.0890	uM
N-[3-[1-[4-(4-cyanophenyl)phenyl]triazol-4-yl]-1-[(3-hydroxycyclobutyl)amino]-1-oxopropan-2-yl]-1-(2-methylphenyl)cyclopropane-1-carboxamide	2123907: Binding affinity to GST-tagged PIN1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.0930	uM
[(2R)-2-(naphthalene-2-carbonylamino)-3-phenylpropyl] dihydrogen phosphate	1799256: Pin1 Enzymatic Activity Assay from Article 10.1016/j.bmcl.2009.08.034: “Structure-based design of novel human Pin1 inhibitors (I).”	ki	0.1000	uM
(2S)-6-amino-2-[[(6R,9S,12R,19R,22S,25S,28S,31R,34S,37S,40S,43S,46S,49S,52S,55S)-37-benzyl-25,43,46,49,52-pentakis(3-carbamimidamidopropyl)-6,9-bis[(4-fluorophenyl)methyl]-12-[(1S)-1-hydroxyethyl]-28,31-dimethyl-22,40-bis(naphthalen-2-ylmethyl)-4,7,10,13,20,23,26,29,32,35,38,41,44,47,50,53,58,61-octadecaoxo-5,8,11,14,21,24,27,30,33,36,39,42,45,48,51,54,57,62-octadecazatetracyclo[32.26.3.13,59.014,19]tetrahexaconta-1(60),2,59(64)-triene-55-carbonyl]amino]hexanoic acid	1234326: Binding affinity to N-terminal MBP fused and Texas-red-labeled full-length human Pin1 S16A/Y23A mutant expressed in Escherichia coli assessed as increase in fluorescence anisotropy by spectrofluorimetry	kd	0.1200	uM
N-[(E)-1-[1-[4-(4-cyanophenyl)phenyl]triazol-4-yl]-3-(methylamino)-3-oxoprop-1-en-2-yl]-1-(2-methylphenyl)cyclopropane-1-carboxamide	2123907: Binding affinity to GST-tagged PIN1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.1200	uM
N-[3-[1-[4-(4-cyanophenyl)phenyl]triazol-4-yl]-1-[(3-hydroxycyclobutyl)amino]-1-oxopropan-2-yl]-1-phenylcyclopropane-1-carboxamide	2123907: Binding affinity to GST-tagged PIN1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.1300	uM
(2R)-3-(1H-benzimidazol-2-yl)-2-[[5-(4-methoxyphenyl)-2-methylfuran-3-carbonyl]amino]propanoic acid	453509: Inhibition of 8His-tagged Pin1 PPIase domain (45-163)	ic50	0.1300	uM
(2R)-3-(6-fluoro-1H-indol-2-yl)-2-(naphthalene-2-carbonylamino)propanoic acid	1186728: Inhibition of Pin1 (unknown origin)	ki	0.1380	uM
N-[3-[1-[4-(4-cyanophenyl)phenyl]triazol-4-yl]-1-[(1-methylpiperidin-4-yl)amino]-1-oxopropan-2-yl]-1-phenylcyclopropane-1-carboxamide	2123907: Binding affinity to GST-tagged PIN1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.1400	uM
(4S)-5-[(2S)-2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]carbamoyl]piperidin-1-yl]-4-[(2-chloroacetyl)amino]-5-oxopentanoic acid	1975620: Inhibition of Gst-tagged human Pin1 assessed as inhibition constant measured after 12 hrs by FP binding assay	ki	0.1700	uM
[(1R)-1-[(3R,6R,9R,12S,15R,18R,21R,24R,27S,30S)-12-(3-amino-3-oxopropyl)-6,9,15,18,21,24-hexakis[3-(diaminomethylideneamino)propyl]-27-(naphthalen-2-ylmethyl)-2,5,8,11,14,17,20,23,26,29-decaoxo-1,4,7,10,13,16,19,22,25,28-decazabicyclo[28.4.0]tetratriacontan-3-yl]ethyl] dihydrogen phosphate	473215: Binding affinity to human Pin1 S16A/Y23A mutant expressed in Escherichia coli BL21(DE3) by isothermal titration colorimetry	kd	0.1700	uM
(2R)-3-(6-chloro-1H-benzimidazol-2-yl)-2-(naphthalene-2-carbonylamino)propanoic acid	1186728: Inhibition of Pin1 (unknown origin)	ki	0.1730	uM

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
Arsenic Trioxide	decreases expression, increases reaction, affects response to substance, affects cotreatment, decreases reaction (+4 more)	2
Acetaminophen	increases expression, affects response to substance	2
Air Pollutants	increases oxidation, decreases expression, affects cotreatment, increases abundance	2
Tamoxifen	decreases response to substance, affects binding, increases reaction	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
syringic acid	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	increases expression	1
sodium arsenate	decreases expression	1
tetrahydropalmatine	decreases expression	1
arsenite	affects binding, increases reaction	1
manganese chloride	decreases expression, increases abundance	1
4-hydroxy-2-nonenal	affects binding, increases response to substance	1
nickel sulfate	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases expression, decreases reaction	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
U 0126	affects expression, affects reaction	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1

ChEMBL screening assays

176 unique, capped per target: 172 binding, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1046169	Binding	Displacement of WFYpSPFLE from human Pin1 after 10-20 mins by fluorescence polarization assay	Structure-based design of novel human Pin1 inhibitors (I). — Bioorg Med Chem Lett
CHEMBL1738600	Functional	PUBCHEM_BIOASSAY: qHTS Validation Assay to Find Inhibitors of Pin1. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID504591]	PubChem BioAssay data set

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D9W8	Ubigene HGC-27 PIN1 KO	Cancer cell line	Sex unspecified
CVCL_F1QH	HyCyte HGC-27 KO-hPIN1	Cancer cell line	Sex unspecified

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.